Highly Efficient p-Toluenesulfonic Acid-Catalyzed Alcohol Addition or Hydration of Unsymmetrical Arylalkynes

Abstract

Under a catalytic amount of PTSA in aqueous or alcoholic media, activated unsymmetrical arylalkynes 1 undergo regioselective water or alcohol addition to afford successfully carbonyl compounds 2 in good to excellent yields. This new environmentally metal-free procedure, which afforded only Markovnikov adducts, is characterized by the mildness of acidic conditions and the excellent regio- and chemoselectivity.

unsymmetrical arylalkyne - hydration - PTSA - ketone - alcohol addition - water

References

<A NAME="RG16604ST-1A">1a</A> Hudrlik PF. Hudrlik AM. The Chemistry of Carbon-Carbon Triple Bond   Part I:  John Wiley and Sons; New York: 1978. 

<A NAME="RG16604ST-1B">1b</A> Larock LC. Leong WW. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.269 

<A NAME="RG16604ST-2A">2a</A> Kagan HB. Marquett A. Jacques J. Bull. Soc. Chim. Fr.  1960,  1979 

<A NAME="RG16604ST-2B">2b</A> Budde WL. Dessy RE. J. Am. Chem. Soc.  1963,  85:  3964 

<A NAME="RG16604ST-2C">2c</A> Olah GA. Meidar D. Synthesis  1978,  671 

<A NAME="RG16604ST-2D">2d</A> Matsuo K. Urabe K. Izumi Y. Chem. Lett.  1981,  1315 

<A NAME="RG16604ST-2E">2e</A> Amiet G. Hügel HM. Nurlawis F. Synlett  2002,  495 

<A NAME="RG16604ST-2F">2f</A> Nishizawa M. Skwarczynski M. Imagawa H. Sugihara T. Chem. Lett.  2002,  12 

<A NAME="RG16604ST-3A">3a</A> Tokunaga M. Wakatsuki Y. Angew. Chem. Int. Ed.  1998,  37:  2867 

<A NAME="RG16604ST-3B">3b</A> Alavarez P. Basetti M. Gimeno J. Mancini G. Tetrahedron Lett.  2001,  42:  8467 

<A NAME="RG16604ST-3C">3c</A> Taqui Khan MM. Halligudi SB. Shukla S. J. Mol. Catal.  1990,  58:  299 

<A NAME="RG16604ST-3D">3d</A> Setty-Fichman M. Sasson Y. Blum J. J. Mol. Catal. A: Chem.  1997,  126:  27 

<A NAME="RG16604ST-3E">3e</A> Pal M. Parasuraman K. Gupta S. Yeleswarapu KR. Synlett  2002,  1976 

<A NAME="RG16604ST-3F">3f</A> Hiscox W. Jennings PW. Organometallics  1990,  9:  1997 

<A NAME="RG16604ST-3G">3g</A> Hartman JW. Hiscox WC. Jennings PW. J. Org. Chem.  1993,  58:  7613 

<A NAME="RG16604ST-3H">3h</A> Baidossi W. Lahav M. Blum J. J. Org. Chem.  1997,  62:  669 

<A NAME="RG16604ST-3I">3i</A> Israelsohn O. Vollhardt KPC. Blum J. J. Mol. Catal. A: Chem.  2002,  184:  1 

<A NAME="RG16604ST-3J">3j</A> Fukuda Y. Utimoto K. J. Org. Chem.  1991,  56:  3729 

<A NAME="RG16604ST-3K">3k</A> Mizushima E. Sato K. Hayashi T. Tanaka M. Angew. Chem. Int. Ed.  2002,  41:  4563 

<A NAME="RG16604ST-3L">3l</A> Vasudevan A. Verzal MK. Synlett  2004,  631 

<A NAME="RG16604ST-3M">3m</A> Damiano JP. Postel M. J. Organomet. Chem.  1996,  522:  303 

<A NAME="RG16604ST-4A">4a</A> Smith JM. Stewart HW. Roth B. Northey EH. J. Am. Chem. Soc.  1948,  70:  3997 

<A NAME="RG16604ST-4B">4b</A> Allen AD. Chiang Y. Kresge AJ. Tidwell TT. J. Org. Chem.  1982,  47:  775 

<A NAME="RG16604ST-4C">4c</A> Menashe N. Reshef D. Shvo Y. J. Org. Chem.  1991,  56:  2912 

<A NAME="RG16604ST-4D">4d</A> Menashe N. Shvo Y. J. Org. Chem.  1993,  58:  7434 

<A NAME="RG16604ST-5">5</A> Tsuchimoto T. Joya T. Shirakawa E. Kawakami Y. Synlett  2000,  1777 

<A NAME="RG16604ST-6A">6a</A> Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  4467 

<A NAME="RG16604ST-6B">6b</A> Alami M. Ferri F. Linstrumelle G. Tetrahedron Lett.  1993,  34:  6403 

<A NAME="RG16604ST-7">7</A>

Typical Procedure for the PTSA-Catalyzed Hydration of Unsymmetrical Arylalkynes: To a stirred solution of 1a (162 mg, 1 mmol) in 2 mL of absolute EtOH, was added pTSA monohydrate (38 mg, 0.2 mmol). The mixture was heated at reflux for 5 h, diluted with H₂O and extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous Na₂SO₄. After removal of the solvent under vacuo, the crude product was purified by column chromatography on silica gel (CH₂Cl₂) to afford 196 mg (94%) of 2b as a yellow oil. 3-Ethoxy-1-(4-methoxy-phenyl)propan-1-one (2b): ¹H NMR (270 MHz, CDCl₃): δ = 7.89 (2 H, d, J = 8.9 Hz), 6.87 (2 H, d, J = 8.9 Hz), 3.79 (2 H, t, J = 6.8 Hz), 3.78 (3 H, s), 3.47 (2 H, q, J = 7.0 Hz), 3.14 (2 H, t, J = 6.7 Hz), 1.14 (3 H, t, J = 7.0 Hz). ¹³C NMR (67.5 MHz, CDCl₃): δ = 196.7, 163.3, 130.2, 130.0, 113.5, 66.3, 65.8, 55.2, 38.4, 14.9. 1-(4-Aminophenyl)-6-hydroxyhexan-1-one (2f): ¹H NMR (270 MHz, CD₃OD): δ = 7.75 (2 H, d, J = 8.8 Hz), 6.63 (2 H, d, J = 8.8 Hz), 3.55 (2 H, t, J = 6.4 Hz), 2.87 (2 H, t, J = 7.6 Hz), 1.80-1.20 (6 H, m). ¹³C NMR (67.5 MHz, CD₃OD): δ = 201.5, 153.6, 132.1, 126.8, 114.3, 62.3, 38.6, 33.5, 26.7, 26.1. 1-(2-Methoxyphenyl)hexan-1-one (2k): ¹H NMR (270 MHz, CDCl₃): δ = 7.61 (1 H, dd, J = 7.6 Hz, J = 1.8 Hz), 7.45-7.30 (1 H, m), 7.00-6.85 (2 H, m), 3.84 (3 H, s), 2.92 (2 H, t, J = 7.5 Hz), 1.75-1.55 (2 H, m), 1.35-1.25 (4 H, m), 0.87 (3 H, t, J = 6.9 Hz). ¹³C NMR (67.5 MHz, CDCl₃): δ = 202.9, 158.1, 132.8, 129.9, 128.7, 120.4, 111.4, 55.2, 43.5, 31.4, 23.9, 22.3, 13.7.

<A NAME="RG16604ST-8">8</A> For a review see: Swaminathan S. Narayanan KV. Chem. Rev.  1971,  71:  429 

<A NAME="RG16604ST-9A">9a</A> Tzalis D. Koradin C. Knochel P. Tetrahedron Lett.  1999,  40:  6193 

<A NAME="RG16604ST-9B">9b</A> Hartman JW. Sperry L. Tetrahedron Lett.  2004,  45:  3787 

<A NAME="RG16604ST-9C">9c</A> For a review, see: Alonso F. Beletskaya IP. Yus M. Chem. Rev.  2004,  104:  3079